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Aromatase inhibitors (AI) are the gold standard treatment option for hormone-sensitive postmenopausal women with breast cancer. Several studies had documented the accelerated bone loss associated with AI.In this study, we present real-world data describing the efficacy of implementing a comprehensive bone health program to maintain bone mineral density (BMD) in postmenopausal patients with early-stage breast cancer treated with AI.A comprehensive bone health program that includes counseling, exercise, nutritional advice, vitamin D supplements and, when needed, intravenous bisphosphonate infusion was implemented following the initiation of endocrine therapy with AI. Postmenopausal women with hormone-sensitive, early-stage breast cancer treated with endocrine therapy using AI were retrospectively identified. All patients had BMD measurements before and at least 1 year after ET initiation.A total of 210 patients were included, median (range) age 67 (43-86) years. At baseline, osteoporosis was documented in 38 (18.1%) and osteopenia in 101 (48.1%) patients. Despite the known negative effect of AI, 32 (84.2%) patients with baseline osteoporosis and 69 (68.3%) of those with osteopenia, had a stable or better BMD. On the other hand, 41 (57.7%) of those with normal baseline BMD had a drop in their follow up BMD, p 0.001. Vertebral fractures were reported in 3 (11.1%) patients with osteoporosis compared to none in patients with normal BMD, p = 0.021.Despite the known negative effect of ET on bone health of breast cancer patients, implementing a comprehensive bone health program stabilized or improved BMD.

Background Coronavirus disease (COVID–19) has resulted in the death of more than 3.5 million people worldwide. While COVID–19 mostly affects the lungs, different comorbidities can have an impact on its outcomes. We performed an overview of reviews to assess the effect of Chronic Kidney Disease (CKD) on contracting COVID–19, hospitalization, mortality, and disease severity. Methods We searched published and preprint databases. We updated the reviews by searching for primary studies published after August 2020, and prioritized reviews that are most updated and of higher quality using the AMSTAR tool. Results We included 69 systematic reviews and 66 primary studies. Twenty-eight reviews reported on the prevalence of CKD among patients with COVID–19, which ranged from 0.4 to 49.0%. One systematic review showed an increased risk of hospitalization in patients with CKD and COVID–19 (RR = 1.63, 95% CI 1.03–2.58) (Moderate certainty). Primary studies also showed a statistically significant increase of hospitalization in such patients. Thirty-seven systematic reviews assessed mortality risk in patients with CKD and COVID–19. The pooled estimates from primary studies for mortality in patients with CKD and COVID–19 showed a HR of 1.48 (95% CI 1.33–1.65) (Moderate certainty), an OR of 1.77 (95% CI 1.54–2.02) (Moderate certainty) and a RR of 1.6 (95% CI 0.88–2.92) (Low certainty). Conclusions Our review highlights the impact of CKD on the poor outcomes of COVID–19, underscoring the importance of identifying strategies to prevent COVID–19 infection among patients with CKD. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40620-021-01206-8.

Background Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. Objective The IDSA’s goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. Methods A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. Conclusions U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Background: COVID-19–related acute illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. Methods: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. Results: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19–related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. Conclusion: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19–related acute illness.

Introduction: Given the recent advances in early detection, improving access to care and the introduction of more effective anti-cancer medications including endocrine therapy, targeted and immunotherapy, more women with breast cancer survive their disease. Majority of patients with breast cancer express hormone receptors (estrogen and or progesterone receptors) on cancer cells. Aromatase inhibitors (AI) are the gold standard treatment of hormone-sensitive postmenopausal women with breast cancer. Several studies had documented the accelerated bone loss associated with AI. The use of bone modifying agents like bisphosphonates and denosumab had resulted in significant improvement in bone mineral density among females treated with AI. In this paper, we study the efficacy of implementing a comprehensive program on bone health for such patients. Patients and Methods: Postmenopausal women with hormone-sensitive early-stage breast cancer treated with endocrine therapy (ET) were included. A comprehensive bone health program was implemented. The program includes extensive counselling by medical oncologist, calcium and vitamin-D supplements, increase milk intake and exercise. Patients with baseline lumbar spine or total hip T-scores ≥ -2 were given short intravenous bisphosphonate infusion every 6 months. Patients with osteoporosis are referred to and followed in a specially designed “osteoporosis clinic”. Results: Between 2013 and 2019, a total of 210 patients fulfilled the eligibility criteria and were enrolled. All were female, median (range) age 67 (43-86) years. All patients had a pathologically confirmed diagnosis of breast cancer, treated and followed up at our institution. High risk patients (n=103, 49.0%) were treated with 6-8 cycles of chemotherapy, including anthracyclines and taxanes. Following the completion of chemotherapy, all patients were treated with endocrine therapy. Patients with low-risk disease (n=107, 51.0%) were treated with upfront endocrine therapy-alone. Aromatase inhibitors, letrozole or anastrozole, were the endocrine therapy of choice in all patients. At baseline, and prior to start of AI, the median T-scores at the hip and lumber spines were -1.0 (range: -3.6, 1.9) and -1.4 (range: -3.9, 2.6), respectively. Osteoporosis was documented in 38 (18.1%) patients while 101 (48.1%) others had osteopenia; none were on any treatment or even aware of their BMD. 46 (25.3%) patients had vitamin-D deficiency while 74 (40.7%) others had vitamin-D insufficiency and none were on prior active replacement therapy or even aware of this problem. Following at least 12-months of endocrine therapy, 32 (84.2%) of patients with osteoporosis and 69 (68.3%) of those with osteopenia had a stable or higher BMD. Thus, the number of patients with osteoporosis declined to 27, 12.9% of the total cohort. On the other hand, 41 (57.7%) of those with normal baseline BMD had a drop in their follow up BMD. Vertebral fractures, presented with back pain and documented by imaging studies, were reported in 3 (11.1%) patients with osteoporosis compared to none in patients with normal BMD, p=0.021. Rib fracture and hip fracture were reported in one patient each and both had normal BMD before and after AI therapy. Conclusions: Postmenopausal women with breast cancer are at risk of osteopenia and osteoporosis. Such risk increases significantly with the use of AI. However, early interventions with modifiable risk factors, Vitamin-D supplements and use of bone-modifying agents can lower this risk. Citation Format: Razan Mansour, Ula Al-Rasheed, Akram Al-Ibraheem, Shereen Abu Jaradeh, Rashid Abdel-Razeq, Rayan Bater, Noor Mashahdani, Shrouq Tbayshat, Hikmat Abdel-Razeq. The efficacy of a comprehensive bone health program in maintaining bone mineral density in postmenopausal women with early-stage breast cancer treated with endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-30.

Introduction: The Syrian crisis, started in 2011, has had a profound impact on the entire region. Jordan, a low-middle income country with limited resources is ranked first in the region in relation to the number of refugees hosted. The latest national census reported over a million Syrian refugee in the country. Lack of sufficient funding, from either the host country or international refugee aid organizations, may lead to suboptimal treatment of cancer patients. The total number of Syrian cancer patients registered at King Hussein Cancer Center (KHCC) hospital-based cancer registry was 510 patients. Local and regional funds covered the treatment of almost two thirds of these patients. In this study, we report on patterns of presentation and management of Syrian patients with breast cancer treated and followed at our institution. Patients and methods: This is a retrospective data collection of Syrian refugees who presented to our institution with a diagnosis of breast cancer from January 2011 to December 2019. Adult patients aged 18 year or older with pathologically-confirmed diagnosis of breast cancer were required to have at least one medical encounter. Data was collected from the electronic medical records for eligible patients. Management was compared against our approved clinical practice guidelines (CPG). Results: During the study period, a total of 147 adult Syrian refugee patients with breast cancer had at least one medical encounter at our institution. All were females and median age (range) at diagnosis was 47 (21-84) years. Thirty-four (23.1%) patients did not complete the work up and missed subsequent visits and will be excluded from analysis. The remaining 113 patient had biopsy proven invasive (n=110) or ductal carcinoma in situ (n=3) and continued their treatment and follow up; 39 (34.5%) had early stage disease, 48 (42.5%) locally advanced and 26 (23.0%) presented with metastatic disease. Estrogen receptors (ER) were positive in 75 (66.4%) patients while 63 (55.8%) had positive progesterone receptor (PR). HER2 positive disease was documented in 31 (27.4%) while 18 (15.9%) patients had triple negative disease. Eighty (70.8%) patients underwent surgery, 60 (75.0%) were at KHCC. The median time from first encounter to surgery for those who underwent upfront surgery was 2 months. Breast conserving surgery (BCS) was done for 27 (45.0%). However, only 11 (35.4%) of the 31 patients eligible for breast reconstruction underwent such procedure. Adjuvant radiation was given to 49 (77.7%) of 63 candidate patients and some were delayed. Systemic treatment with chemotherapy was given to 103 patients; as neoadjuvant (n=37, 35.9%), adjuvant (n=45, 43.7%) and palliative (n= 21, 20.4%). Among the 31 patients with HER2-positive disease, only 11 (35.5%) patients received it. Additionally, only 3 (30.0%) of 10 patients who were candidates for CDK4/6 inhibitors received it. Genetic Testing and counselling were also suboptimal, only 8 (12.3%) of 65 candidate patients underwent genetic testing. Across all needed treatment, 37 (32.7%) patients had significant deviations when judged against our institutional CPGs. Conclusions: Syrian refugees with breast cancer had late presentation and more advanced-stage disease. They are more likely to receive delayed and suboptimal surgeries, genetic counseling and systemic therapy highlighting the urgent need for international systematic approach for cancer care among such unprivileged population. Citation Format: Hikmat Abdel-Razeq, Faris Tamimi, Maryam El-Atrash, Baha' Sharaf, Razan Mansour, Rawan Mustafa. Late presentation and suboptimal treatment of breast cancer among Syrian refugees. A call for systematic international action [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-73.

Patients with gastric cancer are at higher risk for venous thromboembolic events (VTE). Majority of such patients are treated in ambulatory settings where thromboprophylaxis is not routinely offered. In this study, we report on VTE rates and search for predictors that may help identify patients at higher risk to justify VTE-prophylaxis in ambulatory settings. Patients with pathologically-confirmed gastric adenocarcinoma were retrospectively reviewed for VTE detected by imaging studies. Clinical and pathological features known to increase the risk of VTE were studied. Khorana risk assessment model was applied on patients receiving chemotherapy. A total of 671 patients; median age 55 years, were recruited. VTE were diagnosed in 150 (22.4%) patients, including 42 (28.0%) pulmonary embolism and 18 (12.0%) upper extremity deep vein thrombosis (DVT). Majority (> 80%) developed VTE while in ambulatory settings and none had been on thromboprophylaxis. Rate was higher (27.1%) among 365 patients with metastatic compared to 16.7% among 306 patients with nonmetastatic disease, p = 0.001. Patients with metastatic disease who received multiple lines of chemotherapy (n = 85) had significantly higher rate of VTE compared to those who received a single line; 48.2% versus 19.4%, p

Central nervous system tumors in adolescents and young adults (AYA) are rarely reported in the literature. The association with cancer predisposition syndrome is not established. Programmed death ligand 1 (PD-L1) can predict the potential response of patients to immunotherapy. A link between mismatch repair protein deficiency (MMRP-D) and response to immunotherapy is established. P53 is reported to be positive in MMRD-D cases. We aim to investigate the frequency of MMRP-D in AYA with high-grade glioma and any potential association with PD-L1. A total of 96 cases were tested including 49 (51.0%) cases of glioblastoma. Six cases (6.25%) were MMRP-D, 17 (17.7%) were PD-L1 positive, mostly in grade IV tumors (8.7% in grade III compared to 26% in grade IV, p value = 0.027), and 69 (71.9%) were P3 positive. None of the MMRP-D cases expressed PD-L1. P53-positive cases were mostly MMRP proficient (n = 67; 74.4%, p value 0.051). Fourteen cases (28.7%) were positive for both PD-L1 and P53, while p53-positive grade IV tumors were mostly associated with negative PD-L1 (n = 29, 58%, p value = 0.043). MMRP deficiency does not appear to be prevalent in high-grade glioma in AYA. Expression of PD-L1 in a quarter of cases might suggest a role for immunotherapy in high-grade glioma.

In developing countries, a higher percentage of patients develop cancer at a younger age. Cancer survival rates have significantly improved, highlighting the importance of survivorship programs that address late complications related to cancer itself or its treatment. The purpose of this study is to estimate the prevalence of fertility counseling and sperm banking and related factors among at-risk males newly diagnosed with cancer and planning to receive a potentially curative anticancer therapy. Medical records and hospital database of young male patients with newly diagnosed cancers and planned to start chemotherapy were reviewed for fertility counseling and sperm cryopreservation. Additionally, a self-administered questionnaire was utilized. A total of 186 patients, mean age 32.9 (range: 18–53) years, were included. Non-Hodgkin’s lymphoma 59 (31.7%), leukemia 48 (25.8%), and Hodgkin’s lymphoma 26 (14.0%) were the most common tumors encountered. A total of 129 (75.0%) respondents received fertility counseling prior to their treatment, and this rate was higher among patients with early-stage disease (82.4% vs. 58.1%, p = 0.038). However, sperm banking was performed by 33.1% of the whole study group but was significantly higher among single patients (53.4% vs. 17.7%, p

Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic kidney disease. Studies of ADPKD presented results using different outcome measures. We aimed to summarize outcomes reported in ADPKD studies, including composite outcomes.We conducted a systematic review of published studies that included patients with ADPKD and measured kidney-related outcomes. We searched published databases and included all studies regardless of design with at least 100 participants for observational studies. We excluded studies that were limited to dialysis, transplant, or pregnancy outcomes in patients with ADPKD.This review includes data from 175 published articles (49 randomized controlled trials, 2 interventional clinical trials, 30The finding highlights the inconsistency in the outcomes reported by researchers and how they are measured in ADPKD studies. The variability in the outcomes reported supports the need to standardize outcomes in ADPKD studies.

Background Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long-term prophylaxis. Aim Systematically summarize the evidence on the clinical outcomes of secondary long-term prophylaxis in patients with VWD and severe recurrent bleedings. Methods We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long-term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non-Randomized Studies of interventions (ROBINS-I) tool to assess the quality of the included studies. We conducted random-effects meta-analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR], .24; 95% confidence interval [CI], .17–.35; low certainty evidence), and of epistaxis (RR, .38; 95%CI, .21–.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI .12–59.57; low certainty). Evidence from four before-and-after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR .34; 95%CI, .25–.46; very low certainty evidence). Conclusion VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits.

BackgroundCOVID-19–related acute illness is associated with an increased risk of venous thromboembolism (VTE).ObjectiveThese evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE.MethodsASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment.ResultsThe panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation.ConclusionsThis recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.

Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE. Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.

Immunoassays designed to detect SARS-CoV-2 protein antigens are now commercially available. The most widely used tests are rapid lateral flow assays that generate results in ~15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 antigen (Ag) assays have also been developed. The overall accuracy of SARS-CoV-2 Ag tests, however, is not well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is the third in a series of rapid, frequently updated COVID-19 diagnostic guidelines developed by IDSA. IDSA’s goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 5 diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies. Data on the clinical performance of US Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization are mostly limited to single, one-time testing versus standard nucleic acid amplification testing (NAAT) as the reference standard. Rapid Ag tests have high specificity and low to modest sensitivity compared with reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared with asymptomatic individuals and the time of testing post-onset of symptoms. Based on these observations, rapid reverse transcriptase–polymerase chain reaction (RT-PCR) or laboratory-based NAAT remain the diagnostic methods of choice for diagnosing SARS-CoV-2 infection. However, when molecular testing is not readily available or is logistically infeasible, Ag testing can help identify some individuals with SARS-CoV-2 infection. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Immunoassays designed to detect SARS-CoV-2 protein antigens are now commercially available. The most widely used tests are rapid lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 antigen (Ag) assays have also been developed. The overall accuracy of SARS-CoV-2 Ag tests, however, is not well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is the third in a series of rapid, frequently updated COVID-19 diagnostic guidelines developed by IDSA.IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings.A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations.The panel agreed on five diagnostic recommendations. These recommendations address antigen testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies.Data on the clinical performance of U.S. Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization is mostly limited to single, one-time testing versus standard nucleic acid amplification testing (NAAT) as the reference standard. Rapid Ag tests have high specificity and low to modest sensitivity compared to reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared to asymptomatic individuals and the time of testing post onset of symptoms. Based on these observations, rapid RT-PCR or laboratory-based NAAT remain the diagnostic methods of choice for diagnosing SARS-CoV-2 infection. However, when molecular testing is not readily available or is logistically infeasible, Ag testing can help identify some individuals with SARS-CoV-2 infection. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Sex differences in cancer survival may be related to hormonal changes during puberty and menopause, therefore, we investigated sex differences in the cancer-specific survival rates of children, adolescents and young adults (AYAs), and older adults with sex-nonspecific cancers. We interrogated the November 2019 submission of the SEER 18 database and included microscopically confirmed cases of first primary malignant tumors. We stratified the dataset into children (&lt, 15 years), AYAs (modified, 15–49 years), and older adults (≥50 years). For each age group, we used the Kaplan–Meier method to estimate the sex-stratified 5-year all-site cancer-specific survival probabilities. Of 3,386,276 eligible patients, 45,124 (1.3%) were children, 548,158 (16.2%) were AYAs, and 2,792,994 (82.5%) were older adults. The 5-year all-site cancer-specific survival probabilities were 84.0% (95% CI, 83.5%–84.5%) for boys, 84.8% (95% CI, 84.3%–85.3%) for girls, 70.4% (95% CI, 70.2%–70.6%) for male AYAs, 80.8% (95% CI, 80.6%–81.0%) for female AYAs, 52.0% (95% CI, 51.9%–52.1%) for older adult men, and 52.2% (95% CI, 52.1%–52.3%) for older adult women. The all-site survival rate for female patients with cancer is markedly higher than for male patients with cancer during adolescence and young adulthood, although this difference diminishes in older adulthood.

PURPOSE The epidemiology of cancer in adolescents and young adults (AYAs) is distinct and underinvestigated. Therefore, we investigated the incidence of cancer in AYAs in Jordan. PATIENTS AND METHODS We accessed all records submitted to the Jordan Cancer Registry between 2000 and 2017. We included all patients, age 15-39 years, who were ordinarily resident in Jordan. We then calculated frequencies, age-adjusted incidence rates (AAIRs), and annual percentage changes (APCs) and performed subgroup analyses by biologic sex, age subgroups, and site (SEER AYA site recode/WHO 2008). We also performed site-specific trend analyses using joinpoint models. RESULTS We identified 14,115 eligible patients, of whom 1,531 (10.8%), 4,278 (30.3%), and 8,306 (58.8%) were 15-19, 20-29, and 30-39 years old at diagnosis, respectively. The numbers of male and female AYAs were 5,792 (41.0%) and 8,323 (59.0%), respectively. The crude number of cases increased from 654 in 2000 to 954 in 2017 (APC, 2.6%). The overall AAIR ranged from 32.3 in 2000 to 24.3 in 2017 (APC, –1.7%). The AAIR was 27.6 over the full study period and was higher in females (34.1) than in males (21.6). Carcinomas, lymphomas, and leukemias were the most common cancers. The incidence rates of the majority of cancers trended downward over the study period. CONCLUSION The incidence of cancer in AYAs in Jordan is relatively low and declining. However, the absolute number of cases is increasing because this downtrend does not offset the effect of a high population growth rate; almost a 1,000 cases of cancer are now diagnosed every year, which represents a significant increase in the burden of cancer in a developing country with limited healthcare resources.

Background High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in addition to absolute lymphocyte count (ALC) and other hematologic parameters in association with distant metastases and OS in primary gastric lymphoma (PGL) patients. Methods Clinical data of 139 PGL patients who received treatment at King Hussein Cancer Center (KHCC), Amman-Jordan were retrospectively evaluated. Using data from complete blood count (CBC) tests, the following hematologic parameters: absolute neutrophil count (ANC), ALC, absolute eosinophil count (AEC), absolute monocyte count (AMC), NLR, platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were assessed in association with the following clinical outcomes: presence or absence of baseline distant metastases and OS. We conducted univariate and multivariate analyses assessing the various hematologic parameters in association with distant metastases. Results Univariate and multivariate analyses indicated that patients with an elevated NLR (>3.14) displayed more baseline distant metastases compared to patients with a low NLR (≤3.14), (P value: 0.02 and 0.018, respectively). High baseline ALC (>1,819/µL) was associated with lower baseline distant metastases (P value: 0.04). In the OS analysis, high baseline ANC (>5,100/µL), NLR (>2.75), and PLR (>0.16) were associated with poor OS, (P value: 0.027, 0.016, and 0.011 respectively). Conclusions High NLR and ALC were associated with baseline distant metastases. High baseline ANC, NLR, and PLR were associated with poor OS. Hematologic parameters might be potentially helpful in assessing and correlating NLR with the response success to treatment in PGL.

PURPOSE: The Palestinian Ministry of Health (MoH) routinely refers Palestinian patients with cancer to the King Hussein Cancer Center (KHCC), the largest cancer center in the Middle East. Our aim was to describe the characteristics of these patients.PATIENTS AND METHODS: We performed a retrospective chart review of all Palestinian patients with cancer who were treated at the KHCC during 2018 and 2019. We retrieved data from the Cancer Registry and described the demographic and clinical characteristics of the cohort.RESULTS: Out of 521 Palestinian patients, we excluded 41 patients who were misdiagnosed and included the remaining 480. Most patients were adults (n = 426, 88.8%). The most common cancer sites in men (n = 200) were the hematolymphoid system (n = 47, 23.5%), followed by the digestive system (n = 35, 17.5%), and lung and pleura (n = 23, 11.5%). In women (n = 226), the most common cancer sites were the breast (n = 104, 46.0%), followed by the digestive system (n = 34, 15.0%), and hematolymphoid system (n = 23, 10.2%). Children and adolescents accounted for 11.3% (n = 54) of the total cases. The hematolymphoid system was the most common cancer site (n = 27, 50%), followed by the brain (n = 8, 14.8%). More than a third of all patients presented with distant metastasis.CONCLUSION: The most common cancer sites in our cohort are generally similar to data from the Palestinian territories. Many patients presented with advanced-stage disease, which signals the need for awareness campaigns and screening programs. Cancer is misdiagnosed in many patients with benign tumors, which is a consequence of a shortage in specialists and limited diagnostic equipment.

Background: Coronavirus disease 2019 (COVID-19)–related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19–related critical illness and acute illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19–related critical illness or acute illness who do not have confirmed or suspected VTE. Conclusions: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available., Visual Abstract

BackgroundElevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer.MethodsClinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases.ResultsOn univariate and multivariate analyses patients whom on presentation had high NLR (≥3.3) showed more baseline distant metastases compared to patients with low NLR (ConclusionThis study presents additional evidence of the association of some of the hematologic markers; in particular ANC, NLR, AMC, and MLR, with baseline distant metastases and poor outcome in pancreatic cancer. Whether these immune phenomena can help in identifying patients at higher risk for the subsequent development of distant metastases is unknown.

Ethics are considered a basic aptitude in healthcare, and the capacity to handle ethical dilemmas in tough times calls for an adequate, responsible, and blame-free environment. While do-not-resuscitate (DNR) decisions are made in advance in certain medical situations, in particular in the setting of poor prognosis like in advanced oncology, the discussion of DNR in relation to acute medical conditions, the COVID-19 pandemic in this example, might impose ethical dilemmas to the patient and family, healthcare providers (HCPs) including physicians and nurses, and to the institution. The literature on DNR decisions in the more recent pandemics and outbreaks is scarce. DNR was only discussed amid the H1N1 influenza pandemic in 2009, with clear global recommendations. The unprecedented condition of the COVID-19 pandemic leaves healthcare systems worldwide confronting tough decisions. DNR has been implemented in some countries where the healthcare system is limited in capacity to admit, and thus intubating and resuscitating patients when needed is jeopardized. Some countries were forced to adopt a unilateral DNR policy for certain patient groups. Younger age was used as a discriminator in some, while general medical condition with anticipated good outcome was used in others. The ethical challenge of how to balance patient autonomy vs. beneficence, equality vs. equity, is a pressing concern. In the current difficult situation, when cases top 100 million globally and the death toll surges past 2.7 million, difficult decisions are to be made. Societal rather than individual benefits might prevail. Pre-hospital triaging of cases, engagement of other sectors including mental health specialists and religious scholars to support patients, families, and HCPs in the frontline might help in addressing the psychological stress these groups might encounter in addressing DNR in the current situation.

Medulloepithelioma is a rare brain tumor that has been classified as embryonal tumor with multilayered rosettes (ETMR) if it harbors C19MC amplification. In rare instances, it shows evidence of heterologous differentiation. We report a case of a 10-year-old female who presented with headache, squint, and minimal left sided weakness of 1 week duration. Microscopy revealed a small round blue cell tumor with focal glandular and tubular differentiation. In one focus, well-developed osteoid was identified. The tumor labeled with LIN28A immunostain. Unusual features can be encountered in medulloepithelioma which should be in the differential diagnosis of CNS embryonal tumors. Full description of the case with review of the literature and comparison between cases with and without heterologous elements is presented.

Chemotherapy may cause ovarian toxicity and infertility. Cancer patients are usually overwhelmed, and focus exclusively on cancer diagnosis and may not pay attention to fertility-related issues. In this paper we look at the rate of amenorrhea and fertility counseling among such young patients. Premenopausal women with early-stage breast cancer treated with adjuvant or neoadjuvant chemotherapy were recruited. Amenorrhea was defined as absence of menstruation for ≥12 months after the completion of chemotherapy. A total of 94 patients met the eligibility criteria and were included in this analysis. Median age at diagnosis was 35.7 (range, 22–44) years. Seventy-nine (85.9%) respondents were counseled about amenorrhea and 37 (40.2%) were considering having children. Long-term amenorrhea was reported by 51 (54.3%) patients. The addition of taxanes to anthracyclines, in 2 different regimens, increased the risk of amenorrhea to 69.2% and 66.7% compared to 38.9% with anthracycline-alone, P

Purpose The predictive value of inflammatory parameters as indicators of poor overall survival (OS) has been well studied in various tumors. This study aimed to explore the association of neutrophil-lymphocyte ratio (NLR), among other parameters in upper gastro-intestinal tract tumors with distant metastases and OS. Patients and Methods Retrospective analysis was done for 945 patients (males n= 539, 57.0%) with a median of 57 years (range 19-90 years) treated at King Hussein Cancer Center (KHCC) for gastric (n=501), pancreatic (n=355), and biliary (n=89) carcinoma. NLR, and other parameters were calculated at primary presentation, and the association between the parameters with baseline distant metastases and OS was studied. The optimal cutoff value of NLR was based on receiver operating characteristic curve (ROC) analysis. A prognostic nomogram was then constructed to explore how accurately the OS can be predicted. Results Patients with high baseline NLR (>3.2) had more distant metastases on presentation than patients with low NLR (≤3.2), (p-value

Background: Breast cancer is the most common malignancy among adults in Jordan accounting for 39.4% of all newly diagnosed cancers. Jordan is a lower-middle–income country that lacks national screening program. King Hussein Cancer Foundation/Center (KHCF/KHCC) and Jordan Breast Cancer Program had put significant efforts over past years to increase awareness about breast cancer and improve mammography services. They have introduced two mobile mammography units aiming at reaching women in their local communities, in underserved and underprivileged regions. Aim: Describe the experience of making mammography accessible and free of charge to women in rural and remote areas with limited access to mammography services. Methods: Local health educators were trained to recruit women aged 40 years and above to get free screening mammogram in mobile mammography unit. Data collected from five rural areas in Jordan from 2012 until 2017. Total number is 13570 women. Recall was performed at the fixed mammography unit at KHCC and was free of charge until the diagnosis of cancer affirmed or deferred. Results: The highest percentage of women 55.2% (N: 7733) aged 41-50 years. Women aged less than 40 years were recruited due to their breast-related symptoms. It was ethically difficult to refrain imaging symptomatic women in van in remote areas. However, in areas closer to KHCC symptomatic women with no medical insurance were directly referred to KHCC with voucher for free mammogram and workup. Total number of women referred for screening was 13058 (96.2%) and those referred as diagnostic was 512 (3.8%); their mean age was 48.8 and 45 years respectively. Overall recall rate was 29.3% (N: 3822) among screening cases. Cancer detection rate was 0.85% (N: 112) among screened women and 6.8% (N: 35) among diagnostic cases. Number of women who failed to adhere to follow-up procedures was N=1191 (8.8%). It was noticed that family history of cancer correlated with better adherence to complete follow-up procedures. Conclusion: Mobile mammography unit enabled access to screening mammography in rural areas and also encouraged symptomatic women to seek medical advice early. Ensuring financial coverage may have been an additional motivational factor. Follow-up studies may be conducted to compare tumor size differences between screening and diagnostic cases, prognosis and quality of life.